DESCRIPTION: The objective is to understand how retroviruses lacking an oncogene cause tissue-specific neoplastic disease. The role of the LTR in this process is well-known.One important region within the LTR is the DEN (downstream of enhancer) but its role in pathogenesis is not understood. This element is unique in its ability to induce transcription in activated T cells. Work proposed will first identify the elements within DEN that confer transcriptional activity in activated T cells.Proteins that bind to this region will be identified and the importance of these interactions will be tested using transient expression assays. In aim 2 mutants with large effects identified in Aim 1 will be tested for leukemogenicity in mice. In aim 3, factors that bind to DEN in nonactivated T cells will be identified to test the idea that binding of both constitutive and induced (present in activated T cells only) are important for function of the DEN. Identifying these factors and elucidating their role in pathogenesis should contribute to a broader understanding of gene regulation in T cells.